The invention relates to a diagnostic aid for the scintigraphic visualization of malignant tumors, to a method for the scintigraphic visualization of malignant tumors using this diagnostic aid, and to a process for the preparation of the diagnostic aid.
There has long been a desire to have available a diagnostic aid which allows the size and position of malignant tumors to be established at an early stage. There has been no lack of attempts to attain this object by means of nuclear medical methods which may sensitively detect and provide images of the distribution pattern in the human body of substances coupled to .gamma.-emitting nuclides. The success of these methods depends on whether it is possible to find substances which accumulate specifically or non-specifically in malignant tumors.
It is now hardly possible to keep track of the number of tumor-associated substances which have already been used for tumor scintigraphy, but these substances are not tumor-specific, and their affinity for tumors is often unknown. These include inorganic substrates such as gallium-67 citrate, indium-111 chloride and bismuth-206 chloride. However, products of tumor metabolism, such as nitrogen-13-glutamate and selenium-75-methionine, have also already been used for the detection of tumors by scintigraphy (cf. E. Henze, "Szintigraphische Lokalisationsdiagnostik von Tumoren" (Diagnostic Localization of Tumors by Scintigraphy), Munch. med. Wschr. 127, 182-184 (1985)). Finally, radiolabeled cytostatics such as cobalt-57-bleomycin, or tumor-associated proteins such as iodine-131-antifibrin, have also been used already. It is common to all these substances that they often accumulate in the tumor only in low concentrations, so that unambiguous determination of the position of the tumor is impossible, especially in cases where the tumor foci are small.
However, in recent years tumor scintigraphy has also made considerable advances owing to the availability of radiolabeled, tumor-specific monoclonal antibodies or their immunologically active fragments (cf. A. M. Keenan, J. C. Harbert and S. M. Larson, "Monoclonal Antibodies in Nuclear Medicine", The Journal of Nuclear Medicine, Volume 26, 531-537 (1985)). An improvement in the in vivo kinetics of these antibodies has already produced very encouraging results. The techniques of nuclear medicine which are available permit quantitative and tomographic visualization. However, there has as yet been no extensive clinical experience of the sensitivity, specificity or side effects, because of the heterogeneity of the antibodies which have been used to date. An additional factor is that monoclonal antibodies are able to attach themselves only to the tumors which have the exactly corresponding antigen on the cell surface. Thus, the high specificity of the monoclonal antibodies does not allow general detection of tumors of interest.
Moreover, European Patent Application 142,641 has disclosed an agent for the diagnosis and therapy of tumors which contains an immunomodulator labeled with a radioactive emitter, a dyestuff or a cytostatic. This agent is preferably administered together with a cocktail composed of an aldehyde and an alcohol. The preferred immunomodulators are understood to include muramyldipeptide derivatives, peptidoglycans or peptidoglycan-free extracts from certain bacterial species. Tumor detection was possible in patients who had drunk the said cocktail 30 minutes before administration of the diagnostic aid.